The proposed study is a randomized double-blind, placebo-controlled trial of hydroxyurea, to determine whether vaso-occlusive (painful) crisis rates in patients with sickle cell anemia can be reduced by at least 50%. Recurrent painful crises are the most disabling feature of the disease, interfering with education, vocational training, job retention and psychosocial development. Polymerization of sickle hemoglobin with deoxygenated red cells makes them rigid; vaso-occlusive lesions produced by nondeformable red cells are the cause of painful crises. Fetal hemoglobin (Hb F) interferes with polymerization. The recruitment goal is 286 patients; patients will be followed between 2 and 3 years. Hydroxyurea doses will be gradually increased from 15 mg/kg to the maximum level tolerated by each patient; placebo doses will be adjusted in a similar fashion. Patients and study personnel with direct patient contact will be blinded to treatment assignment. Each crisis reported will be reviewed by an independent committee to assure that it meets study criteria. The primary analysis will be a comparison of crisis attack rates in the treated and control groups. Secondary end point analyses will include comparison of changes in clinical status with changes in Hb F production, comparison of complications of sickle cell anemia in the two treatment groups, and frequency of non-compliance with either regimen. A clinical trial is necessary at this time because clinicians are already using hydroxyurea to treat sickle cell anemia, without proof of efficacy.